De Stefano N, Matthews P M, Fu L, Narayanan S, Stanley J, Francis G S, Antel J P, Arnold D L
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, Quebec, Canada.
Brain. 1998 Aug;121 ( Pt 8):1469-77. doi: 10.1093/brain/121.8.1469.
It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.
在多发性硬化症中，很难在MRI上的全脑T2加权病变体积与临床残疾之间建立强相关性，部分原因是T2加权MRI信号变化缺乏病理特异性。质子磁共振波谱研究表明，测量N-乙酰天门冬氨酸（在成熟大脑中仅定位于神经元和神经突）的共振强度可以提供轴突损伤或功能障碍的特定指标。在此，我们报告了一项对29例复发型或继发进展型临床病程的多发性硬化症患者进行的为期30个月的纵向研究。每隔6 - 8个月进行一次常规脑MRI和单体素质子磁共振波谱检查，并同时进行临床评估。在研究开始时，整个患者组的脑N-乙酰天门冬氨酸:肌酸共振强度比异常低（对照组平均值 = 2.93±0.2，患者组平均值 = 2.56±0.4，P < 0.005）。复发型和继发进展型亚组之间无显著差异。在随访期间，11例复发型患者的脑N-乙酰天门冬氨酸:肌酸比值有下降趋势（8%），且该组患者的脑N-乙酰天门冬氨酸:肌酸比值变化与扩展残疾量表评分之间存在显著相关性（P < 0.001）。对于在30个月随访期间有临床相关复发的患者（11例患者中的7例），这种相关性更为明显。T2加权病变体积增加（整个组在30个月内增加35%，P < 0.0001，亚组之间无差异）在整个患者组或不同亚组中均与残疾无关。我们得出结论，诸如脑N-乙酰天门冬氨酸等轴突损伤或丢失指标可能提供与残疾相关的病理变化的特定测量方法。总的T2加权病变体积虽然比脑N-乙酰天门冬氨酸对时间变化更敏感，但可能与理解残疾进展的相关性较小。
